Although small ring analogs of amino acids display a spectrum of interesting biological properties (e.g. as enzyme inhibitors or as peptidomimetics), there remains a need for stereo- and enantioselective methods by which cyclopropyl and cyclobutyl amino acids can be; prepared. To be useful to the practicing synthetic or bioorganic chemist, such methods must be concise, straightforward, convergent, and capable of introducing the diverse functionality required for biological application. The new methods must also be regio-, stereo-, and enantioselective, and should provide substitution patterns that are currently inaccessible or difficult to prepare. To this end, the Fox group will develop new asymmetric chemistry of cyclopropenes and bicyclobutanes with applications in the synthesis of small ring alpha- and beta-amino acids. The advantage of using cyclopropenes in synthesis is that organometallic reagents can add to the, strained olefin, and the resulting cyclopropylmetal can be trapped with an electrophile. Thus, highly functionalized cyclopropanes with 3 stereocenters can be constructed in one reaction from three simple precursors. Alternatively, enantiomerically enriched cyclopropenes can be used to synthesize bicyclobutanes, and schemes can be devised for introducing biologically relevant functionality while simultaneously releasing the strain of the central bond. However, a number of issues must be addressed for these goals to be realized. Methods must be developed that deliver nucleophiles (or hydride) syn- or anti- relative to the substituent on the 3-position of the cyclopropene, and the enantioselectivity of this addition process must be controlled for cyclopropenes without alkene substituents. A general means for the enantioselective synthesis of cyclopropenes with alkene substituents and methods for synthesizing enantiomerically enriched bicyclobutanes must be devised. Finally, a means for introducing and masking an array of functional groups must be developed. In this proposal, we show that we have made significant progress in addressing the first of these challenges, and we describe how we will accomplish the other goals during the tenure of this grant period.